P1090: LONG TERM FOLLOW-UP OF UNTREATED/RELAPSING MCL PATIENTS WITH THE IBRUTINIB, OBINUTUZUMAB, AND VENETOCLAX COMBINATION.
Authors: Steven Le Gouill, Franck Morschhauser, David Chiron, Kamal Bouabdallah, Guillaume Cartron, Rene Olivier Casasnovas, Caroline Milin, Charles Herbaux, Emmanuelle Tchernonog, Cedric Rossi, Simon Rule, Thomas Gastinne, Mary Callanan, Benoit Tessoulin
Journal: HemaSphere (2023)

Topic: 18. Indolent and mantle-cell non-Hodgkin lymphoma - Clinical Background: Targeted therapies (such as Ibrutinib and Venetoclax) have improved Mantle Cell Lymphoma (MCL) patients’ outcomes. OAsIs trial has evaluated the efficacy and toxicity of the Ibrutinib Obinutuzumab plus venetoclax combination in both R/R and untreated MCL patients (NCT02558816, Le Gouill et al. Blood 2021). Aims: We present updated results with extended follow-ups of patients enrolled in OASIS trial. Methods: The OASIS trial was a 3 arms multicenter prospective phase 1/2 trial. Arm A (n=9) enrolled R/R patients who were treated with Obinutuzumab (Obi, 1000mg) and Ibrutinib (Ibru, 560mg). Patients in Arm B (R/R; n=24) and C (newly diagnosed MCL; n=15) were treated with Obi+Ibru+Venetoclax (Ven, 400mg). Patients’ characteristics have been described in the original manuscript. Results: In cohorts A (n=9) and B (n=24), overall response rates were 89% and 71%, respectively. Median Follow-ups were 72 and 48m, the 4-y PFS were 67% and 50%, respectively. No safety signals appeared during long term FU. Patients who progressed were treated with Bendamustine-containing regimen (6 out of 10) and one patient received Odronextamab and anti-CD22xCD3 bispecific antibodies. For Cohort C (n=15), the median follow-up was 46m (36, 49m). Median PFS and DOR were not reached, the estimated 48m-PFS and 36m-DOR were 80% (Figures 1 & 2). Two patients prematurely discontinued, one early PD (after 4m) and one for Adverse Event (neuropathy after 9m). The early PD patient harbored no adverse event, especially no TP53 alteration. One patient with TP53 mutation is still experiencing disease control. One patient experienced atrial fibrillation and one patient had acute cardiac failure. Regarding infections, one patient died of a progressive multifocal leukoencephalopathy after the completion of treatment. Two patients prematurely discontinued the treatment, one patient had a PD at C4 and has subsequently been treated with R-CHOP, one patient relapsed after treatment completion and has been treated with Glofitamab. In all, 2 patients progressed and 1 died in arm C (PML), hence, the 4-y OS is estimated to be 93%.Figure 1. PFS for STEP-C Cohort (MCL patients at diagnosis, treated with Obin-Ibru-Ven, mFU=41m) Summary/Conclusion: The Ibrutinib-Venetoclax-Obinutuzumab triplet is associated with a sustained disease control, in both R/R (4-y PFS of 50%) and newly diagnosed (4y-PFS of 80%) patients presenting with high risk-profiles (no low-MIPI patients were included in the Oasis Trial). The anti-CD20+Ibrutinib vs anti-CD20+Ibrutinib+Venetoclax combinations are currently under investigation in OASIS-II trial (NCT04802590) for untreated patients with MCL. Keywords: Venetoclax, ibrutinib, Targeted therapy, Mantle cell lymphoma